Machine-Vision-Enabled Salt Dissolution Analysis

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http://hdl.handle.net/10138/321457

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Stukelj , J , Agopov , M , Yliruusi , J , Strachan , C J & Svanbäck , S 2020 , ' Machine-Vision-Enabled Salt Dissolution Analysis ' , Analytical Chemistry , vol. 92 , no. 14 , pp. 9730−9738 . https://doi.org/10.1021/acs.analchem.0c01068

Title: Machine-Vision-Enabled Salt Dissolution Analysis
Author: Stukelj, Jernej; Agopov, Mikael; Yliruusi, Jouko; Strachan, Clare J.; Svanbäck, Sami
Contributor: University of Helsinki, Division of Pharmaceutical Chemistry and Technology
University of Helsinki, The Solubility Company Oy
University of Helsinki, Drug Research Program
University of Helsinki, Division of Pharmaceutical Chemistry and Technology
Date: 2020-07-21
Language: eng
Number of pages: 9
Belongs to series: Analytical Chemistry
ISSN: 0003-2700
URI: http://hdl.handle.net/10138/321457
Abstract: Salt formation is a well-established method to increase the solubility of ionizable drug candidates. However, possible conversion of salt to its original form of free acid or base - disproportionation - can have a drastic effect on the solubility and consequently the bioavailability of a drug. Therefore, during the salt selection process, the salt dissolution behavior should be well understood. Improved understanding could be achieved by a method that enables simultaneous screening of small sample amounts and detailed dissolution process analysis. Here, we use a machine-vision-based single-particle analysis (SPA) method to successfully determine the pH-solubility profile, intrinsic solubility, common-ion effect, pKa, pHmax, and Ksp values of three model compounds in a fast and low sample consumption (<1 mg) manner. Moreover, the SPA method enables, with a particle- scale resolution, in situ observation of the disproportionation process and its immediate effect on the morphology and solubility of dissolving species. In this study, a potentially higher energy thermodynamic solid-state form of diclofenac free acid and an intriguing conversion to liquid verapamil free base were observed upon disproportionation of the respective salts. As such, the SPA method offers a low sample consumption platform for fast yet elaborate characterization of the salt dissolution behavior.
Subject: 116 Chemical sciences
317 Pharmacy
PH-SOLUBILITY PROFILES
WATER-SOLUBLE DRUG
DICLOFENAC SODIUM
MICROENVIRONMENTAL PH
INTRINSIC SOLUBILITY
CARBOXYLIC-ACIDS
THERMAL-ANALYSIS
FORM
TRANSFORMATIONS
THEOPHYLLINE
PH-SOLUBILITY PROFILES
WATER-SOLUBLE DRUG
DICLOFENAC SODIUM
MICROENVIRONMENTAL PH
INTRINSIC SOLUBILITY
CARBOXYLIC-ACIDS
THERMAL-ANALYSIS
FORM
TRANSFORMATIONS
THEOPHYLLINE
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